The US healthcare system is evolving towards a more integrated approach to improving the health of Americans. Greater availability of health insurance through the Affordable Care Act and new organizational models such as integrated healthcare systems are leading health care providers and insurers to consider the totality of costs and benefits, instead of focusing on costs and benefits of individual service delivery silos. For substance users, parity requirements for substance use disorder (SUD) and mental health insurance coverage and health insurance expansion present new opportunities for integrated care. They also present new opportunities and challenges for treating HCV-infected and HIV-infected substance users with highly effective and expensive medications. Both the broad societal economic impact and the health economic benefits for individuals of SUD, HCV, and HIV treatment need to be evaluated and communicated to clinical and policy decision makers in the context of this new environment. The overall specific aim of our P30 Center of Excellence proposal entitled Health Economics of Substance Use Disorder, HCV, and HIV Treatment in the Era of Integrated Health Care is to develop and disseminate economic evidence that informs substance use treatment policy and HCV and HIV care of substance users, and to increase the impact of this research by addressing the needs of integrated healthcare system providers and payers. Our proposed Center (CHERISH: Center for Health Economics of Treatment Interventions for Substance Use Disorder, HCV, and HIV) includes Methodology, HCV and HIV, Dissemination and Policy, Pilot Grant and Training, and Administrative Cores, a Policy Advisory Board, and a Center Advisory Board. The Core leaders and investigators have extensive experience with multi-institutional collaborations and several previous and ongoing collaborations. They will draw on a wider circle of experts involved with each of the NIH-supported research projects. CHERISH will be led by an established national expert in SUD, HCV, and HIV health economic research who has substantial management experience. We will innovatively use web-based technology to supplement frequent in-person meetings and support a structured management process and administrative tracking system. The proposed Center will serve as a national SUD health economics research resource, furthering scientific collaborations among researchers, providing feedback to these researchers from stakeholders, and conducting outreach to clinical and policy decision makers. Such interaction between researchers and decision makers is essential for NIH-funded research on SUD treatment strategies to have its greatest impact. Through pilot grants and associated training activities, we will provide new opportunities for training, mentoring and career development for researchers in the field of SUD, HCV, and HIV health economics. These activities will yield a new cohort of investigators with the skills needed to conduct methodologically sound and innovative SUD economic research to inform SUD, HCV, and HIV treatment policy.